Speech from unfamiliar talkers can be difficult to comprehend initially. These difficulties tend to dissipate with exposure, sometimes within minutes or less. Adaptivity in response to unfamiliar input is now considered a fundamental property of speech perception, and research over the past two decades has made substantial progress in identifying its characteristics. The mechanisms underlying adaptive speech perception, however, remain unknown. Past work has attributed facilitatory effects of exposure to any one of three qualitatively different hypothesized mechanisms: (1) low-level, pre-linguistic, signal normalization, (2) changes in/selection of linguistic representations, or (3) changes in post-perceptual decision-making. Direct comparisons of these hypotheses, or combinations thereof, have been lacking. We describe a general computational framework for adaptive speech perception (ASP) that-for the first time-implements all three mechanisms. We demonstrate how the framework can be used to derive predictions for experiments on perception from the acoustic properties of the stimuli. Using this approach, we find that-at the level of data analysis presently employed by most studies in the field-the signature results of influential experimental paradigms do not distinguish between the three mechanisms. This highlights the need for a change in research practices, so that future experiments provide more informative results. We recommend specific changes to experimental paradigms and data analysis. All data and code for this study are shared via OSF, including the R markdown document that this article is generated from, and an R library that implements the models we present.

Previous intermodulation (IM) studies have employed two (or more) temporal modulations of a stimulus, with different local elements of the stimulus being modulated by different frequencies. Brain activities of IM obtained mainly from electroencephalograms (EEG) have been analyzed in the frequency domain. As a powerful tool, IM, which can provide a direct and objective physiological measure of neural interaction, has emerged as a promising method to decipher neural interactions in visual perception, and reveal the underlying different perceptual processing levels. In this review, we summarize the recent applications of IM in visual perception, detail the protocols and types of IM, and extend its utility and potential applications to the multisensory domain. We propose that using IM could prevail in partially revealing the potential hierarchical processing of multisensory information and contribute to a deeper understanding of the underlying brain dynamics.

The uterus provides protection and nourishment (via its blood supply) to a developing fetus, and contracts to deliver the baby at an appropriate time, thereby having a critical contribution to the life of every human. However, despite this vital role, it is an under-investigated organ, and gaps remain in our understanding of how contractions are initiated or coordinated. The uterus is a smooth muscle organ that undergoes variations in its contractile function in response to hormonal fluctuations, the extreme instance of this being during pregnancy and labor. Researchers typically use various approaches to studying this organ, such as experiments on uterine muscle cells, tissue samples, or the intact organ, or the employment of mathematical models to simulate the electrical, mechanical and ionic activity. The complexity exhibited in the coordinated contractions of the uterus remains a challenge to understand, requiring coordinated solutions from different research fields. This review investigates differences in the underlying physiology between human and common animal models utilized in experiments, and the experimental interventions and computational models used to assess uterine function. We look to a future of hybrid experimental interventions and modeling techniques that could be employed to improve the understanding of the mechanisms enabling the healthy function of the uterus.

Currently, there exist no generally accepted strategies of evaluating computational models for microRNA-disease associations (MDAs). Though K-fold cross validations and case studies seem to be must-have procedures, the value of K, the evaluation metrics, and the choice of query diseases as well as the inclusion of other procedures (such as parameter sensitivity tests, ablation studies and computational cost reports) are all determined on a case-by-case basis and depending on the researchers\' choices. In the current review, we include a comprehensive analysis on how 29 state-of-the-art models for predicting MDAs were evaluated. Based on the analytical results, we recommend a feasible evaluation workflow that would suit any future model to facilitate fair and systematic assessment of predictive performance.

Since the problem proposed in late 2000s, microRNA-disease association (MDA) predictions have been implemented based on the data fusion paradigm. Integrating diverse data sources gains a more comprehensive research perspective, and brings a challenge to algorithm design for generating accurate, concise and consistent representations of the fused data. After more than a decade of research progress, a relatively simple algorithm like the score function or a single computation layer may no longer be sufficient for further improving predictive performance. Advanced model design has become more frequent in recent years, particularly in the form of reasonably combing multiple algorithms, a process known as model fusion. In the current review, we present 29 state-of-the-art models and introduce the taxonomy of computational models for MDA prediction based on model fusion and non-fusion. The new taxonomy exhibits notable changes in the algorithmic architecture of models, compared with that of earlier ones in the 2017 review by Chen et al. Moreover, we discuss the progresses that have been made towards overcoming the obstacles to effective MDA prediction since 2017 and elaborated on how future models can be designed according to a set of new schemas. Lastly, we analysed the strengths and weaknesses of each model category in the proposed taxonomy and proposed future research directions from diverse perspectives for enhancing model performance.

The L-type calcium current ( I CaL ) plays a critical role in cardiac electrophysiology, and models of I CaL are vital tools to predict arrhythmogenicity of drugs and mutations. Five decades of measuring and modeling I CaL have resulted in several competing theories (encoded in mathematical equations). However, the introduction of new models has not typically been accompanied by a data-driven critical comparison with previous work, so that it is unclear which model is best suited for any particular application. In this review, we describe and compare 73 published mammalian I CaL models and use simulated experiments to show that there is a large variability in their predictions, which is not substantially diminished when grouping by species or other categories. We provide model code for 60 models, list major data sources, and discuss experimental and modeling work that will be required to reduce this huge list of competing theories and ultimately develop a community consensus model of I CaL . This article is categorized under: Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Molecular and Cellular Physiology.

Understand what progress has been made toward a functionally predictive lower urinary tract (LUT) model, identify knowledge gaps, and develop from them a path forward.
We surveyed prominent mathematical models of the basic LUT components (bladder, urethra, and their neural control) and categorized the common modeling strategies and theoretical assumptions associated with each component. Given that LUT function emerges from the interaction of these components, we emphasized attempts to model their connections, and highlighted unmodeled aspects of LUT function.
There is currently no satisfactory model of the LUT in its entirety that can predict its function in response to disease, treatment, or other perturbations. In particular, there is a lack of physiologically based mathematical descriptions of the neural control of the LUT.
Based on our survey of the work to date, a potential path to a predictive LUT model is a modular effort in which models are initially built of individual tissue-level components using methods that are extensible and interoperable, allowing them to be connected and tested in a common framework. A modular approach will allow the larger goal of a comprehensive LUT model to be in sight while keeping individual efforts manageable, ensure new models can straightforwardly build on prior research, respect potential interactions between components, and incentivize efforts to model absent components. Using a modular framework and developing models based on physiological principles, to create a functionally predictive model is a challenge that the field is ready to undertake.

Mathematical modelling in glucose metabolism has proven very useful for different reasons. Several models have allowed deeper understanding of the relevant physiological and pathophysiological aspects and promoted new experimental activity to reach increased knowledge of the biological and physiological systems of interest. Glucose metabolism modelling has also proven useful to identify the parameters with specific physiological meaning in single individuals, this being relevant for clinical applications in terms of precision diagnostics or therapy. Among those model-based physiological parameters, an important role resides in those for the assessment of different functional aspects of the pancreatic beta cell. This study focuses on the mathematical models of incretin hormones and other endogenous substances with known effects on insulin secretion and beta-cell function, mainly amino acids, non-esterified fatty acids, and glucagon. We found that there is a relatively large number of mathematical models for the effects on the beta cells of incretin hormones, both at the cellular/organ level or at the higher, whole-body level. In contrast, very few models were identified for the assessment of the effect of other insulin secretagogues. Given the opportunities offered by mathematical modelling, we believe that novel models in the investigated field are certainly advisable.

Polarity-dependent orientation illusions are manifested in figures in which the impression of target orientation does not depend only on geometrical relations between the elements of the figure, but also on the relations between their luminances, that is, on luminance polarities. The best-known phenomenon belonging to this class of effects is the Münsterberg/Café Wall illusion. In this paper a considerable number of examples of this type of illusions are presented, many of which are novel variants. A two-level convolutional model of such illusions is introduced, in which the first level corresponds to the stimulus input and the second level contains units fashioned after simple cells in V1, whose spatial patterns of activity represent the model\'s reaction to the stimulus. The main finding of numerous simulations of the model is that the figures inducing illusory impressions of tilt share a common spatial pattern of neural activation, labeled \'oblique clusters\', which is absent in related non-illusory figures. Furthermore, a similar pattern is also present in simulations of figures which induce veridical impressions of tilt. The simulations suggest that the neural basis of perception of a specific degree of tilt may not be the activity of neurons tuned narrowly to that particular degree of tilt, but rather the presence of certain signature spatial patterns of activity of populations of neurons.

Tissue and organ regeneration is the dynamic process by which a population of cells rearranges into a specific form with specific functions. Traditional tissue regeneration utilizes tissue grafting, cell implantation, and structured scaffolds to achieve clinical efficacy. However, tissue grafting methods face a shortage of donor tissue, while cell implantation may involve leakage of the implanted cells without a supportive 3D matrix. Cell migration, proliferation, and differentiation in structured scaffolds may disorganize and frustrate the artificially pre-designed structures, and sometimes involve immunogenic reactions. To overcome this limitation, the self-organizing properties and innate regenerative capability of tissue/organism formation in the absence of guidance by structured scaffolds has been investigated. This review emphasizes the growing subfield of the regulated self-organizing approach for neotissue formation and describes advances in the subfield using diverse, cutting-edge, inter-disciplinarity technologies. We cohesively summarize the directed self-organization of cells in the micro-engineered cell-ECM system and 3D/4D cell printing. Mathematical modeling of cellular self-organization is also discussed for providing rational guidance to intractable problems in tissue regeneration. It is envisioned that future self-organization approaches integrating biomathematics, micro-nano engineering, and gene circuits developed from synthetic biology will continue to work in concert with self-organizing morphogenesis to enhance rational control during self-organizing in tissue and organ regeneration.